In 2366, the location of the Romulan Neutral Zone was labeled on a tactical intelligence analysis that was displayed on one of the viewscreens of the USS Enterprise-D. (TNG: "The Defector" okudagram)

In 2369, the location of the Romulan Neutral Zone was depicted by a thin line on a Deep Space 9 traffic control database map that was displayed on one of the viewscreens of the Enterprise-D. (TNG: "Birthright, Part II" okudagram)

In 2364, the USS Enterprise-D was ordered to investigate the Neutral Zone to solve a mystery concerning the disappearance of a string of Federation outposts. It was later established that the outposts were destroyed by the Borg due to a signature technique unique to their technology. A crew member aboard the ship, Worf, described it: "The outpost was just not destroyed, it's as though some great force just scooped it off the face of the planet." Later that year, the Enterprise-D encountered a Borg cube that had obliterated several other populations in uncharted space in the same fashion. (TNG: "The Neutral Zone", "Q Who")

In 2366, after receiving intelligence from a Romulan defector about a possible Romulan base at Nelvana III, outposts along the zone received warnings from Starfleet Command. Several independent vessels in nearby sectors received the same warning. (TNG: "The Defector")

According to the Star Trek: Star Charts (p. 66), the first outposts were the Earth Outposts. There were 23 of these outposts, which were established in 2160. The first seven outposts were built in what had been the Romulan War Theater of Operations. Additional outposts were built over the centuries. There were four Tango Outposts in the Bolarus sector, six Sierra Outposts in the Kaleb sector, three Romeo Outposts in the Taugan sector, and six Quebec Outposts in the Hyralan sector.